Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Apr 3;7(1):97.
doi: 10.1186/s40425-019-0582-4.

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Osamu Honjo  1 , Terufumi Kubo  2 , Fumiko Sugaya  3 , Takahiro Nishizaka  4 , Koji Kato  5   6 , Yoshihiko Hirohashi  5 , Hiroki Takahashi  6 , Toshihiko Torigoe  5
Affiliations
Case Reports

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Osamu Honjo et al. J Immunother Cancer. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects.

Case presentation: In this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF.

Conclusion: The severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable, not a trial.

Consent for publication

Appropriate consent was obtained from the patient.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Clinical data and pathological images. a Tumor cells with a pleomorphic appearance but are less cohesive. Hematoxylin and eosin staining; original magnification × 200. b Computed tomography imaging shows a low-intensity lesion measuring approximately 7 cm in S2 of the right lung (left panel). By 4 months after the last nivolumab administration, no distinctive space-occupying lesion is found (right panel). Graphs representing the trends of c platelet count, d LDH and CPK from the time of admission (day 1) to day 16. e Images of the lower extremities at 2 days (left panel), 10 days (center panel), and 2 months (right panel) after the onset of purpura fulminans
See this image and copyright information in PMC

References

    1. Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: immune-related adverse events with use of checkpoint inhibitors for immunotherapy of Cancer. Arthritis Rheumatol. 2017;69:687–699. doi: 10.1002/art.40043. - DOI - PubMed
    1. Malissen N, Lacotte J, Du-Thanh A, Gaudy-Marqueste C, Guillot B, Grob JJ. Macrophage activation syndrome: a new complication of checkpoint inhibitors. Eur J Cancer. 2017;77:88–89. doi: 10.1016/j.ejca.2017.02.016. - DOI - PubMed
    1. Hantel A, Gabster B, Cheng JX, Golomb H, Gajewski TF. Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 2018;6:73. doi: 10.1186/s40425-018-0384-0. - DOI - PMC - PubMed
    1. Sadaat M, Jang S. Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report. J Immunother Cancer. 2018;6:49. doi: 10.1186/s40425-018-0365-3. - DOI - PMC - PubMed
    1. Shah D, Shrestha R, Ramlal R, Hatton J, Saeed H. Pembrolizumab associated hemophagocytic lymphohistiocytosis. Ann Oncol. 2017;28:1403. doi: 10.1093/annonc/mdx113. - DOI - PubMed

Publication types

MeSH terms